Plant-based bioactive molecules for targeting of endoribonuclease using steered molecular dynamic simulation approach: a highly conserved therapeutic target against variants of SARS-CoV-2

Parihar, Arpana; Ahmed, Sayeda Samina; Sharma, Palak; Choudhary, Nishant Kumar; Akter, Farjana; Ali, A.; Sonia, Zannatul Ferdous; Khan, Raju

doi:10.1080/08927022.2022.2113811

Cited by 18 publications

(8 citation statements)

References 54 publications

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“…The reason behind this significant variation in F max peaks for the selected hits is due to the different interaction profiles of the drugs with FemX. Previous in silico and in vitro studies also reported that drugs possess the same dissociation trend during SMD and US. − Lumacaftor and Olaparib possess two and three H-bonds with FemX, respectively. Interaction between Lumacaftor and FemX is mainly stabilized by strong π–π interactions between aromatic residues of receptor and aromatic rings of ligands .…”

Section: Discussionmentioning

confidence: 95%

Targeting Staphylococcal Cell–Wall Biosynthesis Protein FemX Through Steered Molecular Dynamics and Drug-Repurposing Approach

et al. 2023

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Staphylococcus aureus-mediated infection is a serious threat in this antimicrobial-resistant world. S. aureus has become a “superbug” by challenging conventional as well as modern treatment strategies. Nowadays, drug repurposing has become a new trend for the discovery of new drug molecules. This study focuses on evaluating FDA-approved drugs that can be repurposed against S. aureus infection. Steered molecular dynamics (SMD) has been performed for Lumacaftor and Olaparib against staphylococcal FemX to understand their binding to the active site. A time-dependent external force or rupture force has been applied to the ligands to calculate the force required to dislocate the ligand from the binding pocket. SMD analysis indicates that Lumacaftor has a high affinity for the substrate binding pocket in comparison to Olaparib. Umbrella sampling exhibits that Lumacaftor possesses a higher free energy barrier to displace it from the ligand-binding site. The bactericidal activity of Lumacaftor and Olaparib has been tested, and it shows that Lumacaftor has moderate activity along with biofilm inhibition potential (MIC value with conc. 128 μg/mL). Pharmacokinetic and toxicology evaluations indicate that Lumacaftor has higher pharmacokinetic potential with lower toxicity. This is the first experimental report where staphylococcal FemX has been targeted for the discovery of new drugs. It is suggested that Lumacaftor may be a potential lead molecule against S. aureus.

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Section: Discussionmentioning

confidence: 95%

Targeting Staphylococcal Cell–Wall Biosynthesis Protein FemX Through Steered Molecular Dynamics and Drug-Repurposing Approach

et al. 2023

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“…Autodock docking program employs fragmentation approach which promotes the linking of best fragments docked with the receptor binding site by separating the ligand into smaller fragments, further selecting and docking. [30,31] According to the docking energy framework through Autodock, all the ligands; QUETSC, QUEINH, QUENH, QUE2FH, and QUESH were well accommodated in the PPAR-𝛾 binding site and accorded a significant improvement (Figure 2). Upon the associated physicalchemical molecular interactions, the docking scores with interaction residues, bond type, and bond distance are summarized in Table S4 in the Supporting Information.…”

Section: Binding Interaction Profile Of Ppar-𝜸 Ligands With Its Receptormentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Novel Quercetin Derivatives as PPAR‐γ Partial Agonists by Modulating Epithelial–Mesenchymal Transition in Lung Cancer Metastasis

et al. 2023

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Epithelial‐to‐mesenchymal transition (EMT) is responsible for driving metastasis of multiple cancer types including lung cancer. Peroxisome proliferator‐activated receptor (PPAR)‐γ, a ligand‐activated transcription factor, controls expression of variety of genes involved in EMT. Although several synthetic compounds act as potent full agonists for PPAR‐γ, their long term application is restricted due to serious adverse effects. Therefore, partial agonists involving reduced and balanced PPAR‐γ activity are more effective and valued. A previous study discerned the efficacy of quercetin and its derivatives to attain favorable stabilization with PPAR‐γ. Here this work is extended by synthesizing five novel quercetin derivatives (QDs) namely thiosemicarbazone (QUETSC)) and hydrazones (quercetin isonicotinic acid hydrazone (QUEINH), quercetin nicotinic acid hydrazone (QUENH), quercetin 2‐furoic hydrazone (QUE2FH), and quercetin salicyl hydrazone (QUESH)) and their effects are analyzed in modulating EMT in lung cancer cell lines via PPAR‐γ partial activation. QDs‐treated A549 cells diminish cell proliferation strongly at nanomolar concentration compared to NCI‐H460 cells. Of the five screened derivatives, QUETSC, QUE2FH, and QUESH exhibit the property of partial activation as compared to the overexpressive level of rosiglitazone. Consistently, these QDs also suppress EMT process by markedly downregulating the levels of mesenchymal markers (Snail, Slug, and zinc finger E‐box binding homeobox 1) and concomitant upregulation of epithelial marker (E‐cadherin).

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“…The speculative importance of cryopreserved UCB is a core aspect of our ethnographic research. Since UCB banking is often viewed in families as a form of biological protection against potential illnesses, the study aims to explain how appeals to maternal duty for women as mothers are interwoven with expectations about future healthcare and advances in regenerative medicine [196,197] that demand women to do whatever they can for their children.…”

Section: Prospects Challenges and Concluding Remarkmentioning

confidence: 99%

Cryopreservation: A Comprehensive Overview, Challenges, and Future Perspectives

et al. 2023

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Cryopreservation is the most prevalent method of long‐term cell preservation. Effective cell cryopreservation depends on freezing, adequate storage, and correct thawing techniques. Recent advances in cryopreservation techniques minimize the cellular damage which occurs while processing samples. This article focuses on the fundamentals of cryopreservation techniques and how they can be implemented in a variety of clinical settings. The article presents a brief description of each of the standard cryopreservation procedures, such as slow freezing and vitrification. Alongside that, the membrane permeating and nonpermeating cryoprotectants are briefly discussed, along with current advancements in the field of cryopreservation and variables influencing the cryopreservation process. The diminution of cryoinjury incurred by the cell via the resuscitation process will also be highlighted. In the end application of cryopreservation techniques in many fields, with a special emphasis on stem cell preservation techniques and current advancements presented. Furthermore, the challenges while implementing cryopreservation and the futuristic scope of the fields are illustrated herein. The content of this review sheds light on various ways to enhance the output of the cell preservation process and minimize cryoinjury while improving cell revival.

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Plant-based bioactive molecules for targeting of endoribonuclease using steered molecular dynamic simulation approach: a highly conserved therapeutic target against variants of SARS-CoV-2

Cited by 18 publications

References 54 publications

Targeting Staphylococcal Cell–Wall Biosynthesis Protein FemX Through Steered Molecular Dynamics and Drug-Repurposing Approach

Targeting Staphylococcal Cell–Wall Biosynthesis Protein FemX Through Steered Molecular Dynamics and Drug-Repurposing Approach

Design, Synthesis, and Biological Evaluation of Novel Quercetin Derivatives as PPAR‐γ Partial Agonists by Modulating Epithelial–Mesenchymal Transition in Lung Cancer Metastasis

Cryopreservation: A Comprehensive Overview, Challenges, and Future Perspectives

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